The MidasPlus package has proven of great use in designing fullerene based inhibitors of the HIV protease. Our original de-novo design of a low micromolar affinity inhibitor of the HIV protease utilized MIDAS. The refinement of this class of inhibitors has also relied heavily on the use of the Midas package. A feature we have used extensively is the MS module, which generates solvent-accessible molecular surfaces of molecules. We analyzed the files generated by this module to determine changes in the types of surfaces that are exposed to solvent in model complexes of hypothetical fullerene derivatives with the HIV protease. The analysis takes the form of a summation of the amount of hydrophobic surface desolvated by a given derivative. This was compared to surface desolvations of known fullerene inhibitors. If the hypothetical inhibitor showed substantial increases in hydrophobic desolvation relative to the known compound, it was selected as a synthetic target. The result of this analysis was the synthesis of two compounds. Both of these compounds show increased affinity for the HIV protease, relative to our original compound. The two new compounds are both in the nanomolar range, one being in the low nanomolar range. This puts them closer to the therapeutic range.